SH3 (Src Homolgy 3) domains are small protein modules of about 50-60 residues. It is found in proteins involved in several biological processes as diverse as signal transduction pathways, cytoskeleton organization, membrane traffic or organelle assembly. SH3 domains bind to proline-rich peptides that form a left-handed polyproline type II helix (PPII) in one of two opposite orientations. Ligand orientation depends on the position of the positive residue in the target peptide. Peptides that bind in a type I orientation contain the consensus R/KXXPXXP, while the type II orientation conform to the PXXPXR/K consensus.